My research

Alterations in the number and structure of chromosomes are a recurrent feature of many human cancers. The primary mechanism by which they are thought to contribute to the tumor phenotype is either by deregulated expression of genes present in extra copies or by causing loss of tumor suppressor genes. However, genome-wide analyses of thousands of breast cancer specimens have indicated that chromosomal alterations also impact the expression of genes outside rearranged regions, likely by exerting a global effect on the architecture of the genome.

Here, we test this hypothesis by integrating sequencing and microscopy methods to study the effects of chromosomal alterations on global and local nuclear architecture in breast cancer. Using our newly developed method – GPSeq - we will perform genome-wide measurements of DNA loci 3D locations in cell lines that mirror different breast cancer subtypes. We will apply our newly developed hiFISH method to visualize chromosomes at unprecedented resolution, with a particular focus on rearranged regions and by combining it with RNA FISH we will simultaneously measure the local structure and activity of genes that are frequently upregulated in breast cancer.

This study represents a pioneering effort to understand the consequences of cancer-associated chromosomal alterations on the global and local structure and function of the genome, and promises to reveal potentially actionable weaknesses of cancer cells hidden in their 3D genome structure.